Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease

Cystic fibrosis (CF) lung disease manifests through abnormally thick mucus, persistent bacterial infections and a dysregulated innate immune system that involves significant neutrophilic inflammation. Neutrophils, immune cells essential to fight infections, accumulate in large numbers in CF airways...

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Main Authors: Kayla M. Fantone, Naveen Gokanapudi, Balázs Rada
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595994/full
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author Kayla M. Fantone
Naveen Gokanapudi
Balázs Rada
author_facet Kayla M. Fantone
Naveen Gokanapudi
Balázs Rada
author_sort Kayla M. Fantone
collection DOAJ
description Cystic fibrosis (CF) lung disease manifests through abnormally thick mucus, persistent bacterial infections and a dysregulated innate immune system that involves significant neutrophilic inflammation. Neutrophils, immune cells essential to fight infections, accumulate in large numbers in CF airways and release neutrophil extracellular traps (NETs) into the airway lumen that deliver extracellular DNA, granule content and cytokines including IL-1β. Interleukin-1β, a powerful, proinflammatory cytokine, represents another, significant component of the innate immune system that is dysregulated in CF. Both defense mechanisms become problematic as NETs and IL-1β are present at elevated levels in CF airways, potentially creating a destructive cycle that exacerbates lung damage rather than protects against infections. Therefore, understanding the interplay between IL-1β and NETs is crucial for addressing CF lung disease progression. This review examines the general mechanisms of IL-1β release and NET formation, with particular focus on their role in CF lung disease, and proposes that a self-perpetuating, positive feedback loop between these two innate immune processes represents a major driving force in disease progression. This understanding suggests potential therapeutic targets for interrupting the cycle of inflammation and tissue damage in CF airways.
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spelling doaj-art-165dfbfd3f4a42449bc59063cf28734d2025-08-20T03:56:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15959941595994Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung diseaseKayla M. FantoneNaveen GokanapudiBalázs RadaCystic fibrosis (CF) lung disease manifests through abnormally thick mucus, persistent bacterial infections and a dysregulated innate immune system that involves significant neutrophilic inflammation. Neutrophils, immune cells essential to fight infections, accumulate in large numbers in CF airways and release neutrophil extracellular traps (NETs) into the airway lumen that deliver extracellular DNA, granule content and cytokines including IL-1β. Interleukin-1β, a powerful, proinflammatory cytokine, represents another, significant component of the innate immune system that is dysregulated in CF. Both defense mechanisms become problematic as NETs and IL-1β are present at elevated levels in CF airways, potentially creating a destructive cycle that exacerbates lung damage rather than protects against infections. Therefore, understanding the interplay between IL-1β and NETs is crucial for addressing CF lung disease progression. This review examines the general mechanisms of IL-1β release and NET formation, with particular focus on their role in CF lung disease, and proposes that a self-perpetuating, positive feedback loop between these two innate immune processes represents a major driving force in disease progression. This understanding suggests potential therapeutic targets for interrupting the cycle of inflammation and tissue damage in CF airways.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595994/fullcystic fibrosis - CFneutrophil extracellular traps (NET)neutrophillung diseaseinflammasomeinterleukin-1 (IL-1β)
spellingShingle Kayla M. Fantone
Naveen Gokanapudi
Balázs Rada
Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
Frontiers in Immunology
cystic fibrosis - CF
neutrophil extracellular traps (NET)
neutrophil
lung disease
inflammasome
interleukin-1 (IL-1β)
title Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
title_full Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
title_fullStr Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
title_full_unstemmed Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
title_short Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease
title_sort neutrophil extracellular traps and interleukin 1β in cystic fibrosis lung disease
topic cystic fibrosis - CF
neutrophil extracellular traps (NET)
neutrophil
lung disease
inflammasome
interleukin-1 (IL-1β)
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595994/full
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AT naveengokanapudi neutrophilextracellulartrapsandinterleukin1bincysticfibrosislungdisease
AT balazsrada neutrophilextracellulartrapsandinterleukin1bincysticfibrosislungdisease